Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Padmanabha, Das, KM; Wechselberger, L; Liziczai, M; De, la, Rosa, Rodriguez, M; Grabner, GF; Heier, C; Viertlmayr, R; Radler, C; Lichtenegger, J; Zimmermann, R; Borst, JW; Zechner, R; Kersten, S; Oberer, M.
Hypoxia-inducible lipid droplet-associated protein inhibits adipose triglyceride lipase.
J Lipid Res. 2018; 59(3): 531-541.
Doi: 10.1194/jlr.M082388
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- Co-Autor*innen der Med Uni Graz
- Grabner Gernot
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- Abstract:
- Elaborate control mechanisms of intracellular triacylglycerol (TAG) breakdown are critically involved in the maintenance of energy homeostasis. Hypoxia-inducible lipid droplet-associated protein (HILPDA)/hypoxia-inducible gene-2 (Hig-2) has been shown to affect intracellular TAG levels, yet, the underlying molecular mechanisms are unclear. Here, we show that HILPDA inhibits adipose triglyceride lipase (ATGL), the enzyme catalyzing the first step of intracellular TAG hydrolysis. HILPDA shares structural similarity with G0/G1 switch gene 2 (G0S2), an established inhibitor of ATGL. HILPDA inhibits ATGL activity in a dose-dependent manner with an IC50 value of ∼2 μM. ATGL inhibition depends on the direct physical interaction of both proteins and involves the N-terminal hydrophobic region of HILPDA and the N-terminal patatin domain-containing segment of ATGL. Finally, confocal microscopy combined with Förster resonance energy transfer-fluorescence lifetime imaging microscopy analysis indicated that HILPDA and ATGL colocalize and physically interact intracellularly. These findings provide a rational biochemical explanation for the tissue-specific increased TAG accumulation in HILPDA-overexpressing transgenic mouse models.
- Find related publications in this database (using NLM MeSH Indexing)
- Adipocytes - enzymology
- Adipose Tissue - enzymology
- Humans - administration & dosage
- Lipase - antagonists & inhibitors, metabolism
- Neoplasm Proteins - metabolism
- Triglycerides - metabolism
- Find related publications in this database (Keywords)
- hypoxia-inducible gene-2
- intracellular lipolysis
- adipocytes
- lipolysis and fatty acid metabolism
- triglycerides